Bone Physiology

Question 1

Protein in the bone matrix is >90%

Answer 1

Collagen

Question 2

Most abundant cells found in the compact bone are the

Answer 2

Osteocytes

Question 3

An osteoblast becomes an osteocyte when it

Answer 3

Gets trapped in the bone matrix it has secreted

Question 4

Two varieties of bone:

Answer 4

1. Compact2. Trabecular

Question 5

Common site of bone growth, particularly long bones

Answer 5

Epiphysial Plate

Question 6

Three processes that halt bone growth

Answer 6

1. Epiphyses unite with shaft (epiphysial closure)2. Cartilage cells stop proliferating3. VEGF secreted -> vascularization/ ossification

Question 7

Three most important hormone regulators of Calcium in the blood

Answer 7

Parathyroid Hormone (PTH), Vitamin D, calcitonin

Question 8

Transcription Factor associated with osteoblast precursor cells

Answer 8

RUNX 2

Question 9

In mice, knocking out RUNX2 led to

Answer 9

Non-ossification of bones (osteoblasts not maturing) -> floppy mice!

Question 10

Products and enzymes that identify an osteoblast as active

Answer 10

Collagen, Alkaline phosphatase, osteoprotegerin (OPG), RANK ligand

Question 11

These 2 factors from osteoblasts stimulate maturation of an active osteoclast

Answer 11

RANK LIGAND and OPG

Question 12

“Decoy” OPG can bind ________ to inhibit osteoclast differentiation

Answer 12

RANK Ligand

Question 13

In osteoporosis, estrogen replacement therapy will upregulate _____ to inhibit osteoclast activity

Answer 13

OPG

Question 14

Full bone replacement occurs, on average, every

Answer 14

10 years

Question 15

Most of the bodys calcium is in (body part)

Answer 15

Bone (98%)

Question 16

Physiologic roles of Calcium

Answer 16

1. Bone formation
2. Neuronal excitability
3. NT release
4. Muscle contraction
5. Membrane integrity
6. Blood Coagulation

Question 17

Hypocalcemia can lead to:

Answer 17

1. Tetany (increased permeability of neurons to Na+, more action potentials, muscle spasm)
2. Parasthesias (things feel funny)
3. Muscle cramps
4. Convulsions
5. Laryngospasms

Question 18

Hypercalcemia leads to:

Answer 18

Anorexia, Nausea, (GI symptoms basically), lethargy, coma

Question 19

In most cases Calcium and Phosphate are co-regulated, except in

Answer 19

the kidney

(they are regulated in opposite directions)

Question 20

Causes of hypercalcemia

Answer 20

Hyperparathyroidism

Cancer

Question 21

Causes of hypocalcemia

Answer 21

Hypoparathyroidism

Vitamin D Deficiency

Chronic Kidney disease (cant reabsorb in tubules)

Calcium malabsorption

Question 22

How does Vitamin D moderate calcium

Answer 22

Pulls in Ca2+ from gut

Question 23

Mechanism of Phosphorous entrance/exit from body (what mediates)

Answer 23

Phosphorous pulled in from gut w/ help from transporter upregulated by Vitamin D

Filtered in glomerulus, most reabsorbed.

PTH can inhibit resorption transporter (block P, leaves via urine)

Question 24

Causes of hypophosphatemia

Answer 24

Inadequate P absorption (gut disorder or Vitamin D deficiency)

Excessive renal excretion (renal disease/renal failure)

Hyperparathyroidism (too much PTH made, leads to blockage of resabsorption at kidney -> pee too much out)

Question 25

Phosphorous necessary for:

Answer 25

energy (ATP), active enzymes and proteins

Question 26

Causes of hyperphosphatemia

Answer 26

Impaired glomerular filtration (cant get P out of blood) Hypoparathyroidism (PTH not present, too much resorption of P at tubule)

Question 27

What is PTHrP and what does it do?

Answer 27

Protein associated with PTH, binds to the same receptor, though they are usually found in separate places Produced as a "paracrine" hormone in tissues local to the receptor. **_A kind of developmental hormone_** * _Stimulates cartilage cells to proliferate_ and maintain proliferative state (used both in utero bone formation and after birth) * In brain, PTHrP inhibits excitotoxic damage to developing neurons * Critical to teeth eruption

Question 28

In normal circumstances, what is the body's response to low serum calcium?

Answer 28

Parathyroid glands produce more parathyroid hormone, which increases calcium reabsorption in the kidneys. Increase in Vitamin D formation (via liver and kidney) that will "pull in" more calcium from gut. Possible to get bone resorption, but much less common in non-pathogenic people

Question 29

1,25 OHD (Vitamin D) binds to transcalciferin [TC] and then acts on which part of the cell

Answer 29

In the Nucleus, **binds to the RXR** (retanoic acid receptor), which turns off repressors, recruits activators, and **turns on the needed genes to get calcium into the blood**

Question 30

Vitamin D increases _ _, _ _, and _ _ to increase absorption of Calcium from gut and increases expression of enzymes to increase Ca retention at kidney

Answer 30

Calbindins, Ca ATPases, TRPV6 (transporter across lumen)

Question 31

Why would inactive Vitamin D be made?

Answer 31

Plasma calcium too high. As it is being processed, vitamin D shunted towards inactive form until balanced

Question 32

Where is calcitonin made?

Answer 32

Parafollicular Cells in the Thyroid

Question 33

What does calcitonin do, broadly?

Answer 33

Decreases bone breakdown Increases excretion of calcium from kidney **Ultimately wants to reduce serum calcium**

Question 34

What does calcitonin block?

Answer 34

**Blocks osteoclasts** from breaking down bone (and thus releasing calcium into blood).

Question 35

What is the effect of estrogen on osteoclasts?

Answer 35

**estrogen inhibits** secretion of interleukins/ enzymes (IL-1, IL-6, TNF alpha) associated with development of **osteoclasts** **Upregulates OPG** to bind RANK ligand and inhibit osteoclast development Stimulates production of TNF beta that causes **osteoclast apoptosis**

Question 36

Disorders of bone mineral homeostasis (4)

Answer 36

Osteoporosis- overactive osteoclasts due to low estrogen) Osteomalacia (or ricketts)- inadequate mineralization of bones due to Vitamin D deficiency Osteopetrosis- unopposed osteoblasts (osteoclasts not breaking down, leads to "rock bones") Pagets Disease- osteoclasts work abnormally in weird places, leads to abnormal bone remodeling (weird faces)